tacrolimus and Nephrocalcinosis

Calcineurin inhibitors are potent immunosuppressive drugs in solid-organ transplantation and multiple autoimmune diseases. Their use is associated with the acute impairment of glomerular filtration and chronic interstitial fibrosis. The latter is mediated by the accumulation of matrix proteins. In this case report, we present a kidney transplant patient with chronic and progressive allograft failure that was associated with nephrocalcinosis. He did not have hypercalcemic-hypercalciuric states such as hyperparathyroidism, sarcoidosis, and hyper-vitaminosis D; normocalcemic-hypercalciuric states such as distal renal tubular acidosis, medullary sponge kidney, excessive use of high-dose loop diuretics, and beta-thalassemia; hyperphosphaturic conditions; and hyperoxaluria. Moreover, his calcifications were limited to the transplanted kidney and spared the native kidneys and extrarenal tissues, and his renal function had improved and stabilized for 6 months after discontinuation of prolonged-release tacrolimus (Advagraf), indicating a cause and an effect phenomenon. Nephrocalcinosis was suspected after ultrasonography and confirmed by computed tomography scanning. Hence, allograft nephrocalcinosis may indicate chronic tacrolimus nephrotoxicity.

Topics: Humans; Immunosuppressive Agents; Kidney; Male; Nephrocalcinosis; Tacrolimus; Tomography, X-Ray Computed

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.

Topics: Adolescent; Adult; Calcineurin Inhibitors; Calcium Oxalate; Child; Citric Acid; Cyclosporine; Female; Graft Rejection; Humans; Immunosuppressive Agents; Infant; Kidney Failure, Chronic; Kidney Transplantation; Male; Nephrocalcinosis; Postoperative Complications; Risk Factors; Tacrolimus; Urinary Calculi

In this article, we present a case in which marked intratubular calcification occurred in the transplanted kidney. The patient received living renal transplantation without control of severe secondary hyperparathyroidism, and the tacrolimus hydrate was used as an immunosuppressive agent, the adverse effects of which can induce intratubular calcification. Biopsy of the renal allograft revealed many intratubular calcifications in the cortex region of the specimen, although the histological grade was borderline for the Banff classification. The pathogenic causes of intratubular calcification were difficult to distinguish from the adverse effects of tacrolimus and the uncontrolled hyperparathyroidism.

Topics: Biopsy; Female; Humans; Hyperparathyroidism, Secondary; Immunosuppressive Agents; Kidney Transplantation; Kidney Tubules; Middle Aged; Nephrocalcinosis; Tacrolimus